Hippocampus and Memory Systems

Question 1

Bartolomero Eustachi (Eustachius)

Answer 1

1552: created the first illustration of the hippocampus
Paper not published until 1714!!!!
Even used fancy scaling equivalent to what is used in current brain atlases

Question 2

Camillo Golgi

Answer 2

Late 19th century
Chief medical officer at a psychiatric hospital
Metal impregnation of neurons

Question 3

Lorento de Nó

Answer 3

Lorento de Nó named CA1-4

Structure of the Hippocampus

Question 4

history of hippocampus continued
*____ studies in ___(animal)
*Temporal lobe resections in humans
Lesion and resection studies found placidity, bulimia, hypersexuality, loss of sensation… even seizures
Refinement of temporal lobe resections for epilepsy treatment
*Isolated to _____ lobe
*1950s: finally able to come up with structure-function relationships with regards to hippocampal _____
*1952: Brenda Milner at McGill University under the direction of Donald Hebb

Answer 4

Lesion studies in monkeys
Temporal lobe resections in humans
Lesion and resection studies found placidity, bulimia, hypersexuality, loss of sensation… even seizures
Refinement of temporal lobe resections for epilepsy treatment
Isolated to medial temporal lobe

Question 5

Brenda Milner at McGill University under the direction of Donald Hebb

Answer 5

*Encountered two patients (P.B. and F.C.) who had become severely amnesic following unilateral removal of the medial structures of the left temporal lobe for the treatment of epileptic seizures (Penfield and Milner, 1958).
It was proposed that in each case there had been a preexistent, but unsuspected, atrophic lesion in the medial temporal lobe of the opposite hemisphere.
Unilateral surgery would have resulted in a bilateral lesion, an idea that was confirmed at autopsy some years later for patient P.B.
After the two cases were presented at the 1955 meeting of the American Neurological Association, Wilder Penfield (the neurosurgeon in both cases) received a call from William Scoville, a neurosurgeon in Hartford, Connecticut. Brenda Milner sent to see this patient (HM)

Question 6

HM

Answer 6

• Most famous bilateral temporal lobe resection patient
• Knocked down by a bicycle at the age of 7, began to have minor seizures at age 10, and had major seizures after age 16.
• At the age of 27 he had become so incapacitated by his seizures, despite high doses of anticonvulsant medication, that he could not work or lead a normal life.
• Offered H.M. an experimental procedure that he had carried out previously in psychotic patients, and the surgery was then performed with the approval of the patient and his family.
• Post surgery: the epilepsy was now controlled but that his memory impairment was even more severe than in P.B. and F.C.
• Forgot daily events nearly as fast as they occurred
• Absence of any general intellectual loss or perceptual disorder.
• Described his state as “like waking from a dream … every day is alone in itself…” (Milner et al., 1968, p. 217).

Question 7

the first papers said that No Hippo, No Memory (forgetting that other regions are missing)

Answer 7

• Early papers incorrectly cited stating the hippocampus is important for memory
• Surgeon’s description, included the hippocampus, amygdala, and the adjacent parahippocampal gyrus.
• Milner: “Despite the use of the word ‘hippocampal’ in the titles of my papers with Scoville and Penfield, I have never claimed that the memory loss was solely attributable to the hippocampal lesions” (Milner, 1998).
• “It is concluded that the anterior hippocampus and hippocampal gyrus, either separately or together, are critically concerned in the retention of current experience. It is not known whether the amygdala plays any part in this mechanism, since the hippocampal complex has not been removed alone, but always together with uncus and amygdala.”

Question 8

H.M. and the Types of Memory

Answer 8

• Time is not the key factor that determines how long patients like H.M. can retain information in memory.
• The relevant factors are the capacity of immediate memory and attention, i.e., the amount of material that can be held in mind and how successfully it can be rehearsed.
• Psychological distinction between immediate memory and long-term memory is a prominent feature of how the brain has organized its memory functions.

Question 9

3 Principles from H.M. and other patients

Answer 9

• Memory is a distinct cerebral ability separate from other cognitive functions
• Short-term memory and long-term memory are distinct
• Medial temporal love structures are not the ultimate repository of long-term memory

Question 10

H.M. gives us the animal model of hippocampal function
-why do we use animals to study?
what animal is studied now?

Answer 10

Now we have a region of the brain to target
Hippocampus fairly well conserved across mammals
Lesions studies in rats became popular

Question 11

Results of Rat Studies (in regards to memory and hippocampus)

Answer 11

• Rats with hippocampal lesions failed to replicate the deficits seen in H.M.
• Monkeys with hippocampal lesions failed to replicate the deficits seen in H.M.

Question 12

reasons for mistake in thinking that the animal models would result in the same as HM
(2 things)

Answer 12

*1960s and 1970s, not understood that memory and learning could be supported by different brain regions and systems.

• Humans and experimental animals approach similar tasks with different strategies
• Example: Visual Discrimination Tasks/Learning
• -Monkeys learn task gradually over trials by habit learning (basal ganglia-based)
• -Rats perform like monkeys
• -Humans learn task by memorization

Question 13

Animals are People Too… Except When It Comes to Behavior

Answer 13

• To relate behavioral and learning tasks between humans and other animals species, you must be very careful when designing tasks
• Animal analogs of human tests that show deficits
• One-trial visual learning/Match-to-sample with delay
• Delayed nonmatch-to-sample

Question 14

Since then

Answer 14

LTP (1973)
Place cells (1978)
Grid cells
Adult Neurogenesis

Question 15

Hippocampus Across Species

- Non-Mammalian Vertebrates

Answer 15

• In mammals, the hippocampus develops from the edge of the cortex– you need a cortex to form a hippocampus
• Pallium is evolutionary precursor to cortex
• Hippocampal-like structures in birds, reptiles, and fish

Question 16

Bird ‘Hippocampus’ (22-24 slides)

Answer 16

Medial pallium
Does not visually resemble hippocampus
Appear to be multiple variables related to hippocampus size
Food-storing behavior associated with large hippocampi
However, some birds that do not store food also have large hippocampi
Only evolutionary changes in functional or proportional region size can have behavioral consequences, but neither of those correlates with food storing behavior
Can compare more closely related birds to find the rule
Hippocampus size more closely related to food-storing behavior
Narrow-minded in that birds should not have spatial memory abilities only related to food storage

Question 17

Teleost Fish

Answer 17

Forebrain like sock turned inside out
Lateral pallium takes on the role of the hippocampus
Goldfish have strong spatial memory and may build cognitive maps

Question 18

Insects

Answer 18

Olfactory learning and memory
Mushrooms Bodies
Dense network of processes and glia
Associative memory?

Question 19

Octopus

Answer 19

Associative and observational learning
Vertical lobe of brain
Take out –> Lose long-term memory, learning impaired
Add in the Median Superior Frontal Lobe of Brain
Microstructures of parallel fibers produced by small cells
Orthogonally running input fibers
Small set of large output neurons on which all the activity converges
Huge # of synaptic connections
Sample from large field of possibilities
High redundancy of connections

Is this the optimal mechanism for behavioral flexibility????

Question 20

What are the Two Different Ways of Storing Information?

Answer 20

Declarative memory: storage and retrieval of material that is available to consciousness and can be expressed by language (“declared”)

Nondeclarative memory: also known as procedural memory; not available to consciousness with much detail; includes skills and associations that are acquired and retrieved as at unconscious level
“How do you do that?”
“Ummm, I dunno. I just sort of, you know, do.”

Question 21

Declarative memory:

Answer 21

Declarative memory: storage and retrieval of material that is available to consciousness and can be expressed by language (“declared”)

Question 22

Nondeclarative memory

Answer 22

Nondeclarative memory: also known as procedural memory; not available to consciousness with much detail; includes skills and associations that are acquired and retrieved as at unconscious level
“How do you do that?”
“Ummm, I dunno. I just sort of, you know, do.”

Question 23

“How do you do that?”
“Ummm, I dunno. I just sort of, you know, do.”

what type of memory is this?

Answer 23

Nondeclarative memory

Question 24

Problem: Remember Those Other Animals?

2 small issues

Answer 24

Well, they cannot necessarily “declare”
This does not mean they do not have a similar form of memory (and memory system). We just have to adapt classifications to them

slide 33

Question 25

Phylogenetic Memory

Answer 25

Memories that are not memories.. But are memories from the experience of a species over time
Like instinctive behaviors and associations
Based on neuronal connectivity, which changes over time within an individual and a species (natural selection)
*Example: predatory bird shadows causing alarm behavior in baby birds

Question 26

what are the types of Temporal Categories of Memory?

Answer 26

Immediate Memory
Short-term Memory
Long-term Memory

Question 27

Immediate Memory:

-time length

Answer 27

• a couple of seconds
• If I ask you about everything you saw yesterday at some random time, you will only be able to tell me highlights or have no real detail. If I ask you to close your eyes and tell me about what you see around you right now, you can.

Question 28

Short-term Memory

-time length

Answer 28

• seconds to minutes
• Hold in your mind information long enough to achieve some goal (working memory)
• Example: hunting for a lost object. You can work through the house searching for it without researching different areas.

Question 29

Long-term Memory:

Answer 29

*retaining information in more permanent storage (days, weeks, a lifetime)
-Would help you from hunting for a lost object
Things from immediate and short-term memory can be entered into long-term memory consciously or unconsciously
Generally agreed that this requires some sort of change or formation of synapses, as well as gene expression and protein synthesis

Question 30

slide 37: consolidating “traces” into long-term memory

Answer 30

-consolidate immediate into short-term
-consolidate short-term to long-term
-forgetting: to free up space
(lots of things will not get to long term storage)

Question 31

Priming

Answer 31

*A change in the processing of a stimulus due to a previous encounter with the same or related stimulus
-Does not have to reach level of consciousness
*Information stored by priming is not super reliable
-Form associations that may or may not be useful
Resistant to brain injury, aging, and dementia
Does demonstrate that information previously presented is always influential

Question 32

does priming have to reach the level of consciousness?

Answer 32

No

Question 33

is the information learned through priming reliable?

Answer 33

no (not always)

Question 34

Example of Priming

Answer 34

*Get people to work with a list of words under a different context (ex- what type of words are they)
Present them with another word task (ex- fill in the missing letters)
*The words from the first task influence the second task

Question 35

When Priming Leads to “Lies” (when it is not always reliable)

Answer 35

• initial word list has a bunch of candy or baked goods (sweet things)
• people will say that the word “sweet” was on the list

Question 36

Associations are Important

Answer 36

• We are not good at remembering completely arbitrary or meaningless things
• Can improve your ability to learn (and remember) when you try to form associations between things
• Random numbers: normally can only memorize a string of 7 meaningless, arbitrary numbers. Can learn/remember much longer strings if they have meaning (phone numbers) or you try to force meaning onto meaningless things (or use mnemonics)
• Capacity of memory very much linked to what it means to the individual and how it can be linked to other, previously stored information

Question 37

Motivation is also Important

Answer 37

Seems pretty obvious

Example: make people look at pictures of furniture or food. Ask them to identify those pictures from a larger set later. Hungry people more likely to remember the food pictures

(conscious vs less conscious )

Question 38

Conditioned Learning

Answer 38

Generation of a novel response that is elicited by the repeated pairing of a novel stimulus with a stimulus that normally elicits said response

Classical conditioning and Operant conditioning

Question 39

describe Pavlov experiment (what type of conditioning is this?)

Answer 39

Classical conditioning: when an innate reflex is conditioned to a novel stimulus after repeated association with an unrelated stimulus

Question 40

Operant conditioning: (a type of conditioned learning)

• def
• 2 examples

Answer 40

Operant conditioning: increase the probability of a behavioral response after associating with a reward
Example: Thorndike’s cat puzzle box. Cat must learn that pressing a lever leads to freedom and food. Me-wow
Example: Skinner and his rats. Rat must learn to press lever to get food.

Question 41

Classical conditioning: (a type of conditioned learning)

Answer 41

Classical conditioning: when an innate reflex is conditioned to a novel stimulus after repeated association with an unrelated stimulus

Question 42

Forgetting

Answer 42

Extinction: gradual disappearance of conditioning when the reward is no longer provided to reinforce the behavior
Rats and cats not going to press levers recreationally
Forgetting, in general, is important and our brains are really good at it
Less important things more likely to be forgotten
May allow us to retain what is important
Unimportant information can cloud our ability to think over the things that are important

Question 43

Extinction

-def

Answer 43

Extinction: gradual disappearance of conditioning when the reward is no longer provided to reinforce the behavior

Question 44

Amnesia

-types

Answer 44

Pathological forgetting

Anterograde amnesia: inability to establish new memories
Retrograde amnesia: difficulty retrieving old memories

Frequently occurs after neurological insult (trauma/lesions of temporal lobe and diencephalon) or on soap operas and other dramas

Question 45

Brain Systems- Declarative Memory

Answer 45

*Clinical cases have made it clear that the hippocampus and parahippocampal cortex are very important for declarative memory FORMATION
-Damage hippocampus –> anterograde amnesia
*Give someone a list of words to remember
Hippocampus and parahippocampal gyrus activated
Higher activity correlates with better retention
Fun fact- the size of the posterior hippocampus positively correlates with the number of months they have been driving a cab
*Hippocampus and parahippocampal gyrus –> determines transfer of declarative information into long-term memory
Depends on structural and functional changes
*Retrograde amnesia usually follows more generalized lesions/trauma/pathology
-This suggests that the memories are not stored in a singular place
-Memories not stored in hippocampus
*Likely stored in assorted places around the cortex
*1920s: Karl Lashley studied the effects of physically cutting off different regions of the cortex from others
-Found that memory impairment was largely a factor of how much damage was done, not really so much where it was done
-MASS ACTION PRINCIPLE: any amount of degradation of learning and memory depends on the amount of cortex destroyed.
-Also, the more complex the learning task, the more disruptive a lesion is
*Association cortices particularly important
*These sites store information that reflects their function
-Example: Association cortex of the superior temporal lobe area that links speech sounds and their symbolic significance
–Damage –>inability to link words and meanings (Wernicke’s aphasia)
*Neuroimaging studies during recollection of information
-Cortical areas that were activated during the learning phase were reactivated during the recall phase
-Example: different classes of visual images tend to reactivate the same regions of the visual association cortex that were activated during initial perception

Question 46

cab drivers and hippocampus slide 49

Answer 46

-larger posterior hippocampus (taxi drivers) – spatial map

Question 47

Lashley’s experiments

slide 51

Answer 47

FIGURE 30.13 Lashley’s experiments in search of the engram. (A) Lesions of varying size and location (red) were made in rat brains either before or after the animals had learned to run mazes (B) of varying complexity. (C) The reduction in learning Lashley observed was proportional to the amount of tissue destroyed; the lesion locations appear inconsequential. The more complex the learning task, however, the more the lesions affected performance. (After Lashley and Wiley, 1933; Lashley, 1944; and the University of Rome Psychology Lab Website.)

Question 48

Hippocampus and Cortex

Answer 48

-widespread projections from association neocortex converge on the hippocampal region. The output of the hippocampus is ultimately directed back to these same neocortical areas

Question 49

Wernicke’s aphasia

Answer 49

example of association cortices damage

Question 50

memory activation when trying to recall images :T/F

Answer 50

TRUE slide 53

Question 51

Brain Systems- Nondeclarative Memory

-what is involved and what is not involved?

Answer 51

• is involved- Basal ganglia, prefrontal cortex, amygdala, sensory association cortices, cerebellum
• is likely not involved: People with medial temporal lobe damage do not seem to have issues with nondeclarative memory, so those structures are likely not involved
• The role that each plays depends on what specific aspects of nondeclarative memory we are talking about

Question 52

lesion to Sensory Association Cortex

Answer 52

Lesions of the visual association cortex produce impairments in visual priming but leave declarative information intact

Question 53

lesion to Cerebellum

Answer 53

Cerebellum
Lesions here lead to impairment in simple sensorimotor conditioning tasks like classical eye-blink conditioning tasks (tone + air puff)
Connections between basal ganglia and prefrontal cortex
Lesions to either  interferes with ability to learn new motor skills
Huntington’s disease (caudate and putamen)  poor motor skill learning
Parkinson’s disease  poor motor skill learning

Question 54

lesions to Connections between basal ganglia and prefrontal cortex

Answer 54

Lesions to either –> interferes with ability to learn new motor skills

• Huntington’s disease (caudate and putamen) –> poor motor skill learning
• Parkinson’s disease –> poor motor skill learning

Question 55

Parkinson’s Disease and Motor Learning

slide 57

Answer 55

non-declarative memory

Question 56

Declarative vs Nondeclarative

*short-term memory storage –> long-term storage

Answer 56

• declarative: the hippocampus holds it in short term and sends it to long-term
• non-declarative: not sure who is playing the role of the hippocampus

Question 57

Memory and Aging

Answer 57

Everything goes downhill as you age
Brain shrinks as you age
Fewer synapses as you age, but number of cells does not change a lot
Therefore, we think it is the loss of connections that leads to a decrease in learning and memory abilities as you age
These changes may or may not be slowed by “exercising” your brain

Question 58

age-related changes

Answer 58

FIGURE 30.19 Compensatory activation of memory areas in high-functioning older adults. During remembering, activity in prefrontal cortex was restricted to the right prefrontal cortex (following radiological conventions, the brain images are left–right reversed) in both young participants and elderly subjects with poor recall. In contrast, elderly subjects with relatively good memory showed activation in both right and left prefrontal cortex. (After Cabeza et al., 2002.)